Opioids and Road Trauma: Is It the Medicine, the Pain, or Both?

At a time of increasing concern among physicians, public health advocates, and the lay public about the adverse consequences of high-dose opioids for chronic non-cancer pain, new research on the topic has pain investigators talking. This time, the relationship between opioid dose and the risk of involvement with road trauma is under the microscope in a study that has caught the attention of a popular pain listserv run by Linda Watkins, University of Colorado at Boulder, US.

In a population-based study over eight years using data from the Ontario, Canada, public health care system, first author Tara Gomes and colleagues reported that drivers taking 20 mg or more of morphine or its equivalent each day had a 21-42 percent increased risk of road trauma compared to drivers taking lower doses. The new finding appeared online January 14 in JAMA Internal Medicine, along with an accompanying editorial.

A previous population-based study from Gomes and colleagues (Gomes et al., 2011), also using Ontario public health data, found that high doses of opioids (≥200 mg of morphine or equivalent daily) were associated with an almost threefold increased risk of opioid-related mortality compared to lower doses (<20 mg) (also see related editorial by Mark Sullivan (Sullivan, 2011). The new study adds to the ongoing worries about opioid use—particularly high doses of the medications—for persistent non-malignant pain.

In the light of such findings, blaming the opioid is an understandable reaction, but the story is not so simple. For instance, chronic pain itself, which necessitates opioids in the first place, could play an important role in the association between the medications and road trauma. And opioids, of course, also provide relief for many pain sufferers, for whom the barriers to obtaining those medications can severely reduce quality of life.

It is that complicated nature of the issue to which Karen Berkley, an emeritus professor and active researcher at Florida State University, drew the attention of Watkins’ listserv. The ensuing discussion was so interesting that we asked Berkley, and the listserv participants who contributed to that discussion, if we could post their comments on PRF. They agreed—for the benefit of the entire pain research community.

Below is an edited version of their comments, which we hope will generate much further conversation and debate on PRF. Join the discussion by posting a response on PRF today!

Karen's question is a very important one, and well worth discussing. Intuitively, concentration to tasks, including driving, can be compromised by high levels of uncontrolled pain, as much as high doses of opioids can impair function. Where the crossover of pain level and analgesic dosing occurs would be helpful to know for determining maximum functionality and minimum impairment.

There was a study in the late 1990s (see attached slides below on earlier studies on effects of opioids and driving) that looked at cancer patients on >200 mg/day oral morphine equivalent with controlled pain, and compared them to matched cancer patients not on opioids with uncontrolled pain. Study participants performed driving tests, and the ones not on opioids with uncontrolled pain performed worse.

We answered this question in the early 1990s. We did a morphine placebo-controlled motor performance study with cold pressor as the pain source, and performance during the morphine (pain on opioids) was more accurate than during placebo (i.e., pain only). This study was presented at one of the American Pain Society (APS) meetings, but it wasn’t published because the lead author (the person doing the motor performance testing) moved away. Reproducing this study would certainly be important, particularly in chronic pain patients.

One of our published studies following up on this topic showed similar results: Morphine improved pain tolerance of the cold pressor and it did not impair motor, perceptual, or attention tasks (Cleeland et al., 1996).

This issue of the complex factors affecting car crash risk (“accident” is a poor word to use, says the National Highway Traffic Safety Administration [NHTSA]) and the contributions, if any, related to opioid use of any kind are an important issue. We don't need yet another barrier for pain relief, unless we know for sure it's warranted….

It has been shown that many patients with chronic pain have cognitive disorders and reduced hippocampal volume (Hart et al., 2000; Mutso et al., 2012), and rats with neuropathic pain have spatial working memory deficits and LTP impairment in the hippocampus (Ren et al., 2011). Dysfunction of the hippocampus in chronic pain patients may also contribute to road trauma.

I've always included a caution in my Essential Guide to Prescription Drugs morphine profile on driving and hazardous activities and morphine. Having said that, the population involved should be further evaluated. Beyond the effect of untreated pain on driving and incidence of accidents, I would pose that comorbid conditions AND OTC medication and medication combinations be carefully evaluated and stratified by their potential effects. The devil is always in the details…

Acute opioids are expected to have different side effects compared to chronic opioids. Patients on chronic high-dose opioids report functioning at high levels without impairment. Patients on acute opioids routinely report sedation and impairment. A challenge is how any of this correlates with alcohol, which at nearly any dose impairs motor performance—ask an athlete.

In my experience the alternatives to opioids such as the antiepileptics (e.g., gabapentin), and the antidepressants also may impair motor performance. NSAIDs probably do not impair motor performance though they have other well-known toxicities, in particular with chronic use.

Clearly more data are needed but major decisions/changes need to be considered very carefully in light of inadequate data and the many complexities as brought out in this discussion. Sleep impairment is a likely source of driving impairment. So if someone does not sleep because of pain, where is this person on the risk scale? And how do these risks compare to the known risks of alcohol, benzodiazepines, texting, changing CDs or radio stations, having a 2-year-old crying in the back seat, etc.?

How big a problem are we talking about? Of the thousands of traffic deaths each year, in how many is impairment with prescription opioids a potential issue—does anyone know the answer?

The physical and neurologic impact of chronic pain simply has not been explored, in my opinion. For example, pain is a major risk factor for falls and medications are not a factor in that risk. People with chronic pain do have heightened reflex activity and those reflexes will be active whether or not the patient is taking opioids. Certainly opioids can increase the risk of complications but to ignore the disease of chronic pain and its impact on physiologic functioning is not good science. I have been talking with patients for 30 years about falls triggered by the disease of chronic pain. Falls happen suddenly and without warning and when, among chronic back pain patients, you really pin the patient down to the physical events that led to the fall, the fall almost always occurs during activities that induce an axial torque on the spine. Comments from patients suggest that these torques trigger a variable intensity flexor withdrawal reflex that disrupts balance. The typical comment, unsolicited, is that it was as if the leg just wasn't there. The same events could theoretically occur during driving and driving a car does involve significant axial torque on the spine.

Secondly, the JAMA Internal Medicine article by Gomes et al. does not provide a database that will account for the frequency with which chronic pain patients, and especially the high-dose opioid pain patients, stop driving on their own volition or limit driving to bare necessities. Patients who are living in chronic pain are truly isolated and by and large invisible to the traditional medical models for analyzing epidemiologic data.

It is easy to count beans whether the cause is opioid-related or non-opioid-related and some bean counting needs to be done. However, it is much more difficult to measure the impact of a poorly understood disease like chronic pain on the lives of a largely invisible population.